Study on Spectral Method and Computational Simulation of Chlorinated Bisphenol Compound and Thyroxine-Binding Globulin

摘要

Bisphenol A(BPA)and chlorinated derivatives(Chlorinated bisphenol A,Cl-BPA)are recognized as chemicals that destroy the endocrine system and widely exist in the environment.Because theirs structure is similar to thyroxin,it can compete after binding with Cl-BPA were studied by fluorescence spectroscopy,Forster resonance energy transfer,Fourier transform infrared spectroscopy,molecular docking and quantum chemistry.The results of fluorescence experiments show that Cl-BPA can quench the fluorescence of TBG by static quenching and non-radiative energy transfer.The number of binding sites(n)of Cl-BPA-TBG complex is about 1,and the binding constant(Ka)is greater than 1.00×10~6 L·mol~(-1).Combined with thermodynamic parameter analysis and molecular docking analysis,Cl-BPA can bind to TBG through hydrogen bonding and hydrophobicity.Quantum chemical analysis further confirmed that the oxygen atoms in Cl-BPA compounds are easy to form hydrogen bonding forces with NH and OH in TBG.Further molecular dynamics simulation analysis showed that the protein structure changed after Cl-BPA combined with TBG.In this study,we have a deep understanding of the interaction mechanism between Cl-BPA and thyroid protein through various spectral experiments and computer simulation methods.Introduction Thyroxine binding globulin(TBG)is a member of the serine protease inhibitor(serpin)superfamily(also known as SERPINA7).TBG differs from other serine protease inhibitors in that the upper part of the β-sheet is fully opened.Therefore,the reactive central peptide ring can be easily moved into and out of the folded sheet to promote the binding and release of the thyroid hormone(TH).[1] TBG is a very important carrier protein for transporting TH in the human blood.Improper molecular folding or changes in the core of peptides will change the secretion of TBG,the binding ability of TBG to TH,and the immunoreactivity produced by the body.[2] Studies have shown that TBG is thought to help provide iodine to fetuses that initially have no iodine reserve.Therefore,it is expected that the replacement of Thyroxine(T4)from the TBG transporter complex during development may have an impact on fetal development and subsequent adulthood.[3] Bisphenol A(BPA)is used as an intermediate for bonding,plasticizing and